Attenuated Bordetella pertussis vaccine candidate BPZE1 promotes human dendritic cell CCL21-induced migration and drives a Th1/Th17 response
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Updated: Jun 3, 2026
Evaluation of Host-Pathogen Responses and Vaccine Efficacy in Mice
Published on: February 22, 2019
Giorgio Fedele1, Manuela Bianco, Anne-Sophie Debrie
1Dipartimento di Malattie Infettive, Parassitarie ed Immunomediate, Istituto Superiore di Sanità, 00161 Rome, Italy. giorgio.fedele@iss.it
Insights
A new live attenuated pertussis vaccine, BPZE1, activates human dendritic cells, promoting immune responses. BPZE1-primed cells migrate effectively, potentially offering robust protection against pertussis in neonates.
Area of Science:
- Immunology
- Vaccinology
- Microbiology
Background:
- Pertussis (whooping cough) remains a threat, especially to neonates, necessitating improved vaccines.
- Existing vaccines may not provide complete or long-lasting immunity from the first dose.
- A novel live attenuated *Bordetella pertussis* strain, BPZE1, was developed by removing key virulence factors.
Purpose of the Study:
- To evaluate the immunogenicity of the novel live attenuated *Bordetella pertussis* vaccine strain, BPZE1.
- To assess BPZE1's impact on human monocyte-derived dendritic cell (MDDC) function.
- To investigate how BPZE1-primed dendritic cells regulate T helper (Th) and suppressor T cells (Ts).
Main Methods:
- Utilized a human preclinical ex vivo model with monocyte-derived dendritic cells (MDDCs).
- Assessed MDDC activation, cytokine production, and migration in response to BPZE1.
- Studied the regulatory effects of BPZE1-primed MDDCs on Th and Ts cells using Transwell systems.
Main Results:
- BPZE1 activated human MDDCs, inducing a range of pro-inflammatory and regulatory cytokines.
- BPZE1-primed MDDCs exhibited enhanced migration towards CCL21 compared to wild-type strains, due to inactivated pertussis toxin.
- BPZE1-primed MDDCs promoted a mixed Th1/Th17 polarization and induced functional Ts cells, with suppression requiring cell contact.
Conclusions:
- BPZE1 demonstrates potential as a live attenuated pertussis vaccine.
- BPZE1-challenged dendritic cells may migrate to lymph nodes to prime T cells.
- The vaccine could orchestrate adaptive immune responses, including Th1/Th17 and Ts cell induction, for effective pertussis control.
Abstract:
New vaccines against pertussis are needed to evoke full protection and long-lasting immunological memory starting from the first administration in neonates--the major target of the life-threatening pertussis infection. A novel live attenuated Bordetella pertussis vaccine strain, BPZE1, has been developed by eliminating or detoxifying three important B. pertussis virulence factors: pertussis toxin, dermonecrotic toxin, and tracheal cytotoxin. We used a human preclinical ex vivo model based on monocyte-derived dendritic cells (MDDCs) to evaluate BPZE1 immunogenicity. We studied the effects of BPZE1 on MDDC functions, focusing on the impact of Bordetella-primed dendritic cells in the regulation of Th and suppressor T cells (Ts). BPZE1 is able to activate human MDDCs and to promote the production of a broad spectrum of proinflammatory and regulatory cytokines. Moreover, conversely to its parental wild-type counterpart BPSM, BPZE1-primed MDDCs very efficiently migrate in vitro in response to the lymphatic chemokine CCL21, due to the inactivation of pertussis toxin enzymatic activity. BPZE1-primed MDDCs drove a mixed Th1/Th17 polarization and also induced functional Ts. Experiments performed in a Transwell system showed that cell contact rather than the production of soluble factors was required for suppression activity. Overall, our findings support the potential of BPZE1 as a novel live attenuated pertussis vaccine, as BPZE1-challenged dendritic cells might migrate from the site of infection to the lymph nodes, prime Th cells, mount an adaptive immune response, and orchestrate Th1/Th17 and Ts responses.
